EP0517797B1 - Use of vitamin-d analogues in the treatment of acne - Google Patents

Use of vitamin-d analogues in the treatment of acne Download PDF

Info

Publication number
EP0517797B1
EP0517797B1 EP91905594A EP91905594A EP0517797B1 EP 0517797 B1 EP0517797 B1 EP 0517797B1 EP 91905594 A EP91905594 A EP 91905594A EP 91905594 A EP91905594 A EP 91905594A EP 0517797 B1 EP0517797 B1 EP 0517797B1
Authority
EP
European Patent Office
Prior art keywords
acne
vitamin
treatment
pct
preparations
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP91905594A
Other languages
German (de)
French (fr)
Other versions
EP0517797A1 (en
Inventor
Wagn Ole Godtfredsen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Leo Pharma AS
Original Assignee
Leo Pharmaceutical Products Ltd AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Leo Pharmaceutical Products Ltd AS filed Critical Leo Pharmaceutical Products Ltd AS
Publication of EP0517797A1 publication Critical patent/EP0517797A1/en
Application granted granted Critical
Publication of EP0517797B1 publication Critical patent/EP0517797B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders

Definitions

  • This invention relates to the use of the vitamin D analogue MC 903; 1 S ,1' E ,3 R ,5 Z ,7 E ,20 R )-(9,10)-seco-20-(3'-cyclopropyl-3'-hydroxyprop-1'-enyl)-1,3-dihydroxypregna-5,7,10(19)-triene in the preparation of a pharmaceutical preparation for the treatment of acne.
  • transdermal absorption after topical application of 1 ⁇ ,25-(OH)2D3 or systemic treatment with this compound may, due to its potent calcemic activity, give rise to undesired effects leading to hypercalcemia.
  • vitamin D analogue which has only moderate activity on calcium metabolism compared to 1,25-(OH)2D3, but having retained the ability to activate receptors for 1,25-(OH)2D3 not associated with calcium absorption or bone calcium mobilization it is possible to treat acne successfully without having the risk of inducing hypercalcemia.
  • the vitamin D analogue for use in the present pharmaceutical preparations is a compound described in international patent application No. PCT/DK86/00081, international filing date 14th July, 1986, International Publication No. WO 87/00834 designated MC 903 (example 5 in said patent application) (confer also Calverley, M., Tetrahedron 43 , 4609-4619 (1987); Binderup, L. and Bramm, E., Biochemical Pharmacology 37 , 889-895 (1988)).
  • the mentioned compound shall form part of pharmaceutical preparations, in particular for topical use, which are useful in the treatment of human disorders as described above, such as a liniment, a lotion or a cream which in addition to the vitamin D analogue in question may contain further active ingredients.
  • concentration of the active ingredient will generally be between 1 and 100 ⁇ g/g.
  • the formulations will be applied once or twice daily for prolonged periods of time.
  • formulations prepared according to the present invention comprise the active compound in association with a pharmaceutically acceptable carrier therefore and optionally other therapeutic ingredient(s).
  • the carrier(s) must be "acceptable” in the sense of being compatible with the other ingredients of the preparations and not deleterious to the recipient thereof.
  • the preparations may conveniently be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active compound into association with the carrier which constitutes one or more accessory ingredients. In general, the preparations are prepared by uniformly and intimately bringing the active compound into association with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product into the desired preparation.
  • Preparations suitable for topical administration include liquid or semi-liquid preparations such as liniments, lotions, applicants, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes; or solutions or suspensions such as drops.
  • the preparations of this invention may include one or more additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • the preparations may, as mentioned above, contain further therapeutically active compounds usually applied in the above mentioned treatment.
  • ointments, creams, or lotions containing from 1-100 ⁇ g/g of the vitamin D analogue or metabolites are administered.
  • Preparations of the present invention suitable for oral administration may be in the form of discrete units as capsules, sachets, tablets or lozenges, each containing a predetermined amount of the active compound; in the form of a powder or granules; in the form of a solution or a suspension in an aqueous liquid or non-aqueous liquid; or in the form of an oil-in-water emulsion or a water-in-oil emulsion.
  • the active compound may also be administered in the form of a bolus, electuary or paste.
  • a tablet may be made by compressing or moulding the active compound optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing, in a suitable machine, the active compound in a free-flowing form such as a powder or granules, optionally mixed by a binder, lubricant, inert diluent, surface active or dispersing agent.
  • Moulded tablets may be made by moulding, in a suitable machine, a mixture of the powdered active compound and suitable carrier moistened with an inert liquid diluent.
  • Preparations for rectal administration may be in the form of a suppository incorporating the active compound and a carrier such as cocoa butter, or in the form of an enema.
  • Preparations suitable for parenteral administration conveniently comprise a sterile oily or aqueous preparation of the active compound which is preferably isotonic with the blood of the recipient.
  • the preparations of this invention may include one or more additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • the oral preparations are formulated, preferably as tablets, capsules, or drops, containing from 0.5-1000 ⁇ g of the vitamin D analogue or metabolites, per dosage unit.
  • Example 2 Cream containing 50 ⁇ g MC 903/g
  • Dissolve MC903 in a solution of glycerol, disodium hydrogenphosphate, sodium dihydrogenphosphate and polyoxyethylene stearylether dissolved in water. Mix with the melted cetomacrogol 1000, liquid paraffin, cetostearyl alcohol and white petrolatum. Homogenize the emulsion and cool. Dissolve chloroallylhexaminium chloride in part of the water and mix until homogeneous with the emulsion. Fill the cream in aluminium tubes.
  • Example 3 Cream containing 100 ⁇ g MC 903/g
  • MC903 100 mg Cetomacrogol 1000 30 g Cetostearyl alcohol 60 g Chloroallylhexaminium chloride 0.5 g Propylenglycol 30 g Disodium hydrogenphosphate 2 g Sodium dihydrogenphosphate 0.1 g Liquid paraffin 50 g White petrolatum 170 g Purified water up to 1000 g
  • Example 5 Use of MC 903 lotion in the treatment of acne vulgaris of the face

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)
  • Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)

Abstract

PCT No. PCT/DK91/00056 Sec. 371 Date Jun. 11, 1992 Sec. 102(e) Date Jun. 11, 1992 PCT Filed Feb. 25, 1991 PCT Pub. No. WO91/12807 PCT Pub. Date Sep. 5, 1991.The present invention relates to the use of certain vitamin D analogues in the preparation of a pharmaceutical preparation for the treatment of acne. The preparation contains a vitamin D analogue (calcipotriol) which has only moderate activity on the calcium metabolism when compared to 1,25-(OH)2 D3, but has retained the ability to activate receptors for 1,25-(OH)2 D3 not associated with calcium absorption or bone calcium mobilization.

Description

  • This invention relates to the use of the vitamin D analogue MC 903;
       1S,1'E,3R,5Z,7E,20R)-(9,10)-seco-20-(3'-cyclopropyl-3'-hydroxyprop-1'-enyl)-1,3-dihydroxypregna-5,7,10(19)-triene
    in the preparation of a pharmaceutical preparation for the treatment of acne.
  • Among the factors contributing to the aetiology of acne, an increased sebum production appears to be of major importance, as the severity of the acne parallels sebum excretion rates.
  • In accordance with this, the reduction of sebum production induced by treatment with oestrogens or isotretinoin leads to an improvement in acne. However, the hormonal effects of the former precludes its widespread use, and isotretinoin is teratogenic and is only used for very severe acne due to this and other side effects (Drug and Therapeutics Bulletin, Vol. 22, No. 24, December 3, 1984).
  • Recently it has been found that topical application of 1α,25-dihydroxyvitamin D₃ (1α,25-(OH)₂D₃) reduces the size of sebaceous glands in the ear of male Syrian hamsters (V.L. Malloy et al, The tricontinental Meeting for Investigative Dermatology, Washington, USA, 1989).
  • However, this observation may be of limited utility in the human medicine because transdermal absorption after topical application of 1α,25-(OH)₂D₃ or systemic treatment with this compound, may, due to its potent calcemic activity, give rise to undesired effects leading to hypercalcemia.
  • However, by choosing a vitamin D analogue which has only moderate activity on calcium metabolism compared to 1,25-(OH)₂D₃, but having retained the ability to activate receptors for 1,25-(OH)₂D₃ not associated with calcium absorption or bone calcium mobilization it is possible to treat acne successfully without having the risk of inducing hypercalcemia.
  • The vitamin D analogue for use in the present pharmaceutical preparations is a compound described in international patent application No. PCT/DK86/00081, international filing date 14th July, 1986, International Publication No. WO 87/00834 designated MC 903 (example 5 in said patent application) (confer also Calverley, M., Tetrahedron 43, 4609-4619 (1987); Binderup, L. and Bramm, E., Biochemical Pharmacology 37, 889-895 (1988)).
  • The mentioned compound shall form part of pharmaceutical preparations, in particular for topical use, which are useful in the treatment of human disorders as described above, such as a liniment, a lotion or a cream which in addition to the vitamin D analogue in question may contain further active ingredients. The concentration of the active ingredient will generally be between 1 and 100 µg/g.
  • The formulations will be applied once or twice daily for prolonged periods of time.
  • The formulations prepared according to the present invention comprise the active compound in association with a pharmaceutically acceptable carrier therefore and optionally other therapeutic ingredient(s). The carrier(s) must be "acceptable" in the sense of being compatible with the other ingredients of the preparations and not deleterious to the recipient thereof.
  • The preparations may conveniently be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active compound into association with the carrier which constitutes one or more accessory ingredients. In general, the preparations are prepared by uniformly and intimately bringing the active compound into association with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product into the desired preparation.
  • Preparations suitable for topical administration include liquid or semi-liquid preparations such as liniments, lotions, applicants, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes; or solutions or suspensions such as drops.
  • In addition to the aforementioned ingredients, the preparations of this invention may include one or more additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • The preparations may, as mentioned above, contain further therapeutically active compounds usually applied in the above mentioned treatment.
  • In the topical treatment, ointments, creams, or lotions containing from 1-100 µg/g of the vitamin D analogue or metabolites are administered.
  • Preparations of the present invention suitable for oral administration may be in the form of discrete units as capsules, sachets, tablets or lozenges, each containing a predetermined amount of the active compound; in the form of a powder or granules; in the form of a solution or a suspension in an aqueous liquid or non-aqueous liquid; or in the form of an oil-in-water emulsion or a water-in-oil emulsion. The active compound may also be administered in the form of a bolus, electuary or paste.
  • A tablet may be made by compressing or moulding the active compound optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing, in a suitable machine, the active compound in a free-flowing form such as a powder or granules, optionally mixed by a binder, lubricant, inert diluent, surface active or dispersing agent. Moulded tablets may be made by moulding, in a suitable machine, a mixture of the powdered active compound and suitable carrier moistened with an inert liquid diluent.
  • Preparations for rectal administration may be in the form of a suppository incorporating the active compound and a carrier such as cocoa butter, or in the form of an enema.
  • Preparations suitable for parenteral administration conveniently comprise a sterile oily or aqueous preparation of the active compound which is preferably isotonic with the blood of the recipient.
  • In addition to the aforementioned ingredients, the preparations of this invention may include one or more additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • The oral preparations are formulated, preferably as tablets, capsules, or drops, containing from 0.5-1000 µg of the vitamin D analogue or metabolites, per dosage unit.
  • The invention will now be further described in the following non-limiting Examples:
    • Example 1 Cream Containing MC 903
  • In 1 g almond oil was dissolved 1 mg MC 903. To this solution was added 40 g of mineral oil and 20 g of self-emulsifying beeswax. The mixture was heated to liquify. After the addition of 40 ml hot water, the mixture was mixed well. The resulting cream contains approximately 10 µg of MC 903 per gram of cream.
    • Example 2 Cream containing 50 µg MC 903/g
  • MC903 50 mg
    Cetomacrogol 1000 25 g
    Cetostearyl alcohol 75 g
    Chloroallylhexaminium chloride 0.5 g
    Glycerol 30 g
    Disodium hydrogenphosphate 2 g
    Sodium dihydrogenphosphate 0.1 g
    Liquid paraffin 60 g
    Polyoxyethylene stearylether 12 g
    White petrolatum 160 g
    Purified water up to 1000 g
  • Dissolve MC903 in a solution of glycerol, disodium hydrogenphosphate, sodium dihydrogenphosphate and polyoxyethylene stearylether dissolved in water. Mix with the melted cetomacrogol 1000, liquid paraffin, cetostearyl alcohol and white petrolatum. Homogenize the emulsion and cool. Dissolve chloroallylhexaminium chloride in part of the water and mix until homogeneous with the emulsion. Fill the cream in aluminium tubes.
    • Example 3 Cream containing 100 µg MC 903/g
  • MC903 100 mg
    Cetomacrogol 1000 30 g
    Cetostearyl alcohol 60 g
    Chloroallylhexaminium chloride 0.5 g
    Propylenglycol 30 g
    Disodium hydrogenphosphate 2 g
    Sodium dihydrogenphosphate 0.1 g
    Liquid paraffin 50 g
    White petrolatum 170 g
    Purified water up to 1000 g
  • Melt cetomacrogol 1000, cetostearyl alcohol, liquid paraffin and white petrolatum at 75°C. Dissolve propylenglycol in water at 75°C and mix the solution with the fatty phase. Homogenize the emulsion and cool to 30°C. Mill MC903 to particle size below 5µm and suspend in an aqueous solution of disodium hydrogenphosphate, sodium dihydrogenphosphate and chloroallylhexaminium chloride. Add the suspension to the emulsion and fill the cream in tubes.
    • Example 4 Lotion containing 50 µg MC 903/g
  • MC903 50 mg
    Absolute alcohol 400 g
    Hydroxypropylcellulose 1 g
    Menthol 1 g
    Sodium citrate 1 g
    Propylenglycol 40 g
    Purified water up to 1000 ml
  • Dissolve hydroxypropylcellulose, sodium citrate and propylenglycol in water. Mix with a solution of MC903 and menthol in absolute alcohol. Fill the lotion in polyethylen plastic bottles.
    • Example 5 Use of MC 903 lotion in the treatment of acne vulgaris of the face
  • A total of 10 patients with acne vulgaris of the face have been assessed in an open, non-controlled study of MC 903 lotion. Patients were treated for up to 6 weeks with twice daily applications of the lotion: 50 µg/ml. The study provided evidence that MC 903 lotion was well tolerated. Furthermore, the data pertaining to the therapeutic efficacy of the lotion are encouraging.

Claims (3)

  1. The use of the compound MC 903:
       1S,1'E,3R,5Z,7E,20R)-(9,10)-seco-20-(3'-cyclopropyl-3'-hydroxyprop-1'-enyl)-1,3-dihydroxypregna-5,7,10(19)-triene
    in the manufacture of a medicament for the treatment of acne.
  2. The use according to claim 1 wherein the medicament is provided for topical application containing the active component as defined in claim 1 in an amount of from 1 to 100 µg/g of the medicament.
  3. The use according to claim 1 wherein the medicament is provided for oral application containing the active ingredient as defined in claim 1 in an amount of from 0.5 to 1000 µg per dosage unit.
EP91905594A 1990-03-01 1991-02-25 Use of vitamin-d analogues in the treatment of acne Expired - Lifetime EP0517797B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9004544 1990-03-01
GB909004544A GB9004544D0 (en) 1990-03-01 1990-03-01 Novel treatment ii
PCT/DK1991/000056 WO1991012807A1 (en) 1990-03-01 1991-02-25 Use of vitamin-d analogues in the treatment of acne

Publications (2)

Publication Number Publication Date
EP0517797A1 EP0517797A1 (en) 1992-12-16
EP0517797B1 true EP0517797B1 (en) 1995-09-13

Family

ID=10671792

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91905594A Expired - Lifetime EP0517797B1 (en) 1990-03-01 1991-02-25 Use of vitamin-d analogues in the treatment of acne

Country Status (11)

Country Link
US (1) US5292727A (en)
EP (1) EP0517797B1 (en)
JP (1) JPH05504959A (en)
AT (1) ATE127691T1 (en)
AU (1) AU7458891A (en)
DE (1) DE69113029T2 (en)
DK (1) DK0517797T3 (en)
ES (1) ES2079063T3 (en)
GB (1) GB9004544D0 (en)
GR (1) GR3017413T3 (en)
WO (1) WO1991012807A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2186269C2 (en) * 2000-02-25 2002-07-27 Дальневосточная государственная морская академия им. адмирала Г.И. Невельского Method of production of antifriction coat on thin- walled steel inserts of sliding bases
RU2201542C2 (en) * 1996-10-14 2003-03-27 Сосьете Насьональ Д'Этюд Э Де Констрюксьон Де Мотер Д'Авиасьон - С.Н.Е.К.М.А. Braking device component made of composite material cc/sis and its manufacturing process

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5362719A (en) * 1990-03-01 1994-11-08 Leo Pharmaceutical Products, Ltd. A/S Lovens Kemiske Fabrik Produktionsaktieselskab) Use of vitamin-D analogues in the treatment of acne
USRE39706E1 (en) * 1993-01-15 2007-06-26 Leo Pharma A/S Crystalline form of a vitamin D analogue
US5384314B1 (en) * 1994-03-11 1997-08-05 Hoffmann La Roche 1alpha-fluoro-25-hydroxy-16-ene-23-yne-cholecalciferol
PE28297A1 (en) * 1995-01-26 1997-08-20 Hoffmann La Roche DERMATOLOGICAL USE OF VITAMIN D DERIVATIVES
US6491936B1 (en) 1997-12-09 2002-12-10 Chugai Seiyaku Kabushiki Kaisha Creams containing vitamin D3 derivatives
EP1040832A4 (en) * 1997-12-09 2001-09-12 Chugai Pharmaceutical Co Ltd EMULSIONS CONTAINING VITAMIN D 3 DERIVATIVES
AU743582B2 (en) * 1997-12-09 2002-01-31 Chugai Seiyaku Kabushiki Kaisha Lotions containing vitamin D3 derivatives
US8263580B2 (en) * 1998-09-11 2012-09-11 Stiefel Research Australia Pty Ltd Vitamin formulation
ES2388425T5 (en) * 1999-04-23 2020-02-12 Leo Pharma As Non-aqueous pharmaceutical composition for dermal use to treat psoriasis comprising a vitamin D, a corticosteroid and a solvent component
ES2350822T3 (en) * 1999-08-31 2011-01-27 Chugai Seiyaku Kabushiki Kaisha SOFT CAPSULES.
KR100611544B1 (en) * 2000-08-30 2006-08-10 쥬가이 세이야쿠 가부시키가이샤 OCTI formulations
EP1458678A1 (en) * 2002-11-18 2004-09-22 Teva Pharmaceutical Industries Limited A crystallization method for purification of calcipotriene
GB0307865D0 (en) * 2003-04-04 2003-05-14 Novartis Ag Pharmaceutical composition
US7205006B2 (en) * 2003-09-25 2007-04-17 Prime Pharmaceutical Corporation Mahonia aquifolium extract, extraction process and pharmaceutical composition containing the same
FR2871696B1 (en) * 2004-06-17 2006-11-10 Galderma Sa TOPICAL COMPOSITION FOR THE TREATMENT OF PSORIASIS
ES2344989T3 (en) * 2004-11-22 2010-09-13 Wisconsin Alumni Research Foundation ANALOGS OF 17.20 (E) -DESHIDRO VITAMINA D AND ITS USES.
EP1917072B1 (en) 2005-06-01 2013-02-27 Stiefel Research Australia Pty Ltd Vitamin formulation
US20060286054A1 (en) * 2005-06-15 2006-12-21 Apollo Pharmaceutical, Inc. Pharmaceutical compositions for the treatment of psoriasis
CA2882048C (en) 2006-02-03 2020-03-24 Opko Renal, Llc Treating vitamin d insufficiency and deficiency with 25-hydroxyvitamin d2 and 25-hydroxyvitamin d3
HUE037309T2 (en) 2006-06-21 2018-08-28 Opko Ireland Global Holdings Ltd Therapy using vitamin D repletion agent and vitamin D hormone replacement agent
KR20110113664A (en) * 2006-08-29 2011-10-17 테바 파마슈티컬 인더스트리즈 리미티드 Pharmaceutical composition comprising vitamin D and corticosteroids
WO2008073174A2 (en) * 2006-09-08 2008-06-19 The Regents Of The University Of California Antimicrobial therapy
US20100056644A1 (en) * 2006-11-29 2010-03-04 Nilendu Sen Pharmaceutical compositions containing anhydrous calcipotriene
ES2401205T3 (en) * 2007-04-25 2013-04-17 Cytochroma Inc. Oral controlled release compositions comprising a vitamin D compound and a waxy support
CA2684778C (en) 2007-04-25 2017-09-05 Cytochroma Inc. Methods and compounds for vitamin d therapy
CA2683514C (en) 2007-04-25 2019-07-09 Proventiv Therapeutics, Llc Method of safely and effectively treating and preventing secondary hyperparathyroidism in chronic kidney disease
WO2009047644A2 (en) 2007-04-25 2009-04-16 Cytochroma Inc. Method of treating vitamin d insufficiency and deficiency
US7727562B2 (en) * 2007-06-21 2010-06-01 Blackman Steven T Liquid compositions containing solubilized benzoyl peroxide
KR101685031B1 (en) 2008-04-02 2016-12-09 사이토크로마 인코포레이티드 Methods, compositions, uses, and kits useful for vitamin d deficiency and related disorders
CN103037902A (en) 2010-03-29 2013-04-10 赛特克罗公司 Methods and compositions for reducing parathyroid levels
JP5652723B2 (en) * 2012-08-17 2015-01-14 フォーモサ・ラボラトリーズ・インコーポレーテッド New crystal form of maxacalcitol
JP2014144929A (en) * 2013-01-29 2014-08-14 Daiichi Sankyo Healthcare Co Ltd Composition containing vitamins for preventing or treating acne
KR101847947B1 (en) 2013-03-15 2018-05-28 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 Stabilized modified release vitamin d formulation
US10220047B2 (en) 2014-08-07 2019-03-05 Opko Ireland Global Holdings, Ltd. Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
EP4596045A3 (en) 2016-03-28 2025-10-15 EirGen Pharma Ltd. Methods of vitamin d treatment

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4610978A (en) * 1983-03-22 1986-09-09 Yissum Research Development Company Of The Hebrew University Of Jerusalem Compositions containing 1α-hydroxycholecalciferol for topical treatment of skin disorders and methods employing same
GB2183156B (en) * 1985-03-14 1989-06-21 Chugai Pharmaceutical Co Ltd Composition for treating skin disease
US5145846A (en) * 1988-01-20 1992-09-08 Hoffmann-La Roche Inc. Vitamin D3 analogs
US5104864A (en) * 1988-08-02 1992-04-14 Bone Care International, Inc. Method for treating and preventing loss of bone mass
EP0398217B1 (en) * 1989-05-18 1994-01-12 F. Hoffmann-La Roche Ag Dehydrocholecalciferol derivatives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
WO 87/00834 *
WO 89/10351 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2201542C2 (en) * 1996-10-14 2003-03-27 Сосьете Насьональ Д'Этюд Э Де Констрюксьон Де Мотер Д'Авиасьон - С.Н.Е.К.М.А. Braking device component made of composite material cc/sis and its manufacturing process
RU2186269C2 (en) * 2000-02-25 2002-07-27 Дальневосточная государственная морская академия им. адмирала Г.И. Невельского Method of production of antifriction coat on thin- walled steel inserts of sliding bases

Also Published As

Publication number Publication date
WO1991012807A1 (en) 1991-09-05
EP0517797A1 (en) 1992-12-16
US5292727A (en) 1994-03-08
DE69113029D1 (en) 1995-10-19
ES2079063T3 (en) 1996-01-01
DE69113029T2 (en) 1996-03-07
AU7458891A (en) 1991-09-18
GB9004544D0 (en) 1990-04-25
JPH05504959A (en) 1993-07-29
GR3017413T3 (en) 1995-12-31
DK0517797T3 (en) 1995-11-13
ATE127691T1 (en) 1995-09-15

Similar Documents

Publication Publication Date Title
US5292727A (en) Use of the treatment of acne
JP4955895B2 (en) Use of 2α-methyl-19-nor-20 (S) -1α, 25-dihydroxyvitamin D3 to increase bone strength
AU2001273303A1 (en) Use of 2alpha-methyl-19-nor-20(s)-1alpha,25-dihydroxyvitamin D3 to increase bone strength
MXPA04007618A (en) 1-alpha-hydroxy-2-methylene-19-nor-pregnacalciferol and its uses.
AU678800B2 (en) Hydroxy vitamin D3 compounds for treating skin atrophy
US5362719A (en) Use of vitamin-D analogues in the treatment of acne
CA2416194C (en) Use of 2-methylene-19-nor-20(s)-1.alpha.,25-dihydroxyvitamin d3 to increase bone strength
AU2001278888A1 (en) Use of 2-methylene-19-nor-20(s)-1alpha,25-dihydroxyvitamin D3 to increase bone strength
AU5595698A (en) Method of treating prostatic diseases using active vitamin d analogues
AU705895B2 (en) Use of 19-nor-vitamin d compounds for the prevention of hyperphosphatemia in kidney disorder patients
EP1722856B1 (en) Use of 2-methylene-19-nor-20(s)-1alpha,25-dihydroxyvitamin d3 for the prophylaxis of bone diseases
JP4282234B2 (en) 19-nor-vitamin D3 compound with calcemic activity
WO1990000540A1 (en) The use of vitamin d metabolites or analogues for the prevention of graft rejection
MXPA00011215A (en) 1&agr;-HYDROXY-25-ENE-VITAMIN D, ANALOGS AND USES THEREOF
MXPA98000342A (en) Use of 19-nor-vitamin d compounds for the prevention of hyperphosphatemia in patients with ri disorder

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19920812

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE

17Q First examination report despatched

Effective date: 19930812

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE

REF Corresponds to:

Ref document number: 127691

Country of ref document: AT

Date of ref document: 19950915

Kind code of ref document: T

ITF It: translation for a ep patent filed
REF Corresponds to:

Ref document number: 69113029

Country of ref document: DE

Date of ref document: 19951019

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

REG Reference to a national code

Ref country code: GR

Ref legal event code: FG4A

Free format text: 3017413

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2079063

Country of ref document: ES

Kind code of ref document: T3

ET Fr: translation filed
PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20001125

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20001130

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20001219

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 20001227

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20010112

Year of fee payment: 11

Ref country code: CH

Payment date: 20010112

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LU

Payment date: 20010129

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DK

Payment date: 20010214

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20010223

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20010228

Year of fee payment: 11

Ref country code: AT

Payment date: 20010228

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20010426

Year of fee payment: 11

REG Reference to a national code

Ref country code: GB

Ref legal event code: IF02

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020225

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020225

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020225

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020226

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020226

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020228

Ref country code: DK

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020228

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020228

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020228

BERE Be: lapsed

Owner name: LEO PHARMACEUTICAL PRODUCTS LTD A/S (LOVENS KEMIS

Effective date: 20020228

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020901

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020903

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020909

EUG Se: european patent has lapsed

Ref document number: 91905594.7

REG Reference to a national code

Ref country code: DK

Ref legal event code: EBP

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20020225

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20021031

NLV4 Nl: lapsed or anulled due to non-payment of the annual fee

Effective date: 20020901

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20030922

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050225